EDITORIALS Retinoids and Demethylating Agents— Looking for Partners

The concept that carcinogenesis may be the result of a defi-ciency or a failure of the action of substances that are negative regulators of control of proliferation and growth of cells is hardly new (1) and certainly antedates current interest in the mutation of tumor suppressor genes in the causation of cancer. Thus, in their classic article on the role of retinoid deficiency in control of epithelial proliferation and differentiation, Wolbach and Howe (2) noted that retinoid-deficient epithelial tissues had a premalignant phenotype that was characterized by enhanced mitotic activity and loss of differentiation. Retinoids may indeed be considered prototypes of such negative regulators of epithe-lial cell growth, and there is an immense literature on their mechanism of action and potential use for cancer prevention [reviewed in (3)]. However, although there have been a few major advances i